Helicobacter pylori Infection of Gastric Epithelial Cells Affects NOTCH Pathway In Vitro.

BACKGROUND: Helicobacter pylori infection is exceptionally prevalent, and it is an important risk factor for gastritis, gastroduodenal ulcers, and gastric cancer. However, the pathogenic mechanisms of H. pylori are not entirely clear. The aim of this study was to assess which signal pathway is initially activated by H. pylori.

METHODS: Using the Human Signal Transduction Pathway Finder RT(2) Profiler PCR Array, we screened for alterations in the expression of genes encoding members of ten different signal transduction pathways in GES-1 cells co-cultured with H. pylori. qPCR and Western blotting were used to verify the expression of four key genes in NOTCH pathway.

RESULTS: Of the 84 genes represented in the array, 22 genes demonstrated more than twofold difference (p < 0.05) in GES-1 cells grown in the presence of H. pylori 11637 compared to cells without H. pylori 11637. Ten genes were up-regulated in the co-culture group, whereas 12 appeared to be down-regulated. Further analysis using the SA Biosciences online program revealed that NOTCH pathway was the most significantly affected network. There was a significant reduction in the mRNA expression level of NOTCH1 and NOTCH2, together with a reduced level of active forms of NOTCH1 (NICD1) and NOTCH2 (NICD2). Meanwhile, the expression level of the ligand DLL4 was found to be significantly increased.

CONCLUSIONS: NOTCH signaling may play an important role in H. pylori-induced gastric carcinogenesis.